Cancer Roundup: Updates and commentary on the latest in cancer
By Dr. Ajaz Bulbul
A drug approved for all solid tumors
The US FDA granted an accelerated approval to a new drug, larotrectinib (Vitrakvi), on November 26, 2018; to be available for patients with any solid tumor that has a specific mutation in the (NTRK) fusion gene for those whose disease is metastatic or has spread to multiple organs. This is important because it is the first time FDA has approved a drug solely based on genetic mutation no matter what the site of origin on the tumor is.
In the age of precision medicine where tumors are now studied for genetic variations to determine the best treatment; techniques like molecular sequencing can reveal these mutations and help open up a new treatment option for patients. A total of 12 cancer types may have this mutation like salivary gland tumors, sarcoma, thyroid cancer among others. The overall response rates in at least three clinical three single-arm clinical trials: LOXO-TRK-14001, SCOUT, and NAVIGATE was around 75% with 22% having a complete response.
Two new Acute leukemia drug approvals for elderly patients
After decades of wait, the FDA recently granted accelerated approval to an oral drug called venetoclax (Venclexta) in combination with an infusional treatment already approved for leukemia called azacitidine or decitabine and /or low-dose cytarabine as combination treatment specifically for the treatment of newly diagnosed acute myeloid leukemia (AML) in elderly patients above 75 years or older.
Usually, leukemias are common in elderly, however, due to multiple health conditions and age aggressive, chemotherapy and or transplant is not an option for these patients. High dose chemotherapy and transplant although preferred options have a high degree of complications in older patients. So far, treatment for elderly leukemia has been limited, but with this approval, decent response rates can be seen for these patients and the drug was well tolerated.
In the two M-14 studies that got this treatment approved the complete response (CR) rates were 37-54% when combined with azacytidine and decitabine (non-chemo drugs). The average time to response in the non-chemo arm was up to 5 months. The CR rate with venetoclax with a low-dose chemotherapy drug called Ara-C was 21%. The patients stayed in remission for an average of 4-6 months.
Earlier this month FDA also approved glasdegib (Daurismo) tablets to be used with low-dose cytarabine (AraC) for the treatment of newly diagnosed acute leukemia (AML). The median overall survival was over 8 months for patients treated with the new drug combination glasdegib plus low-dose cytarabine compared with 4.3 months for patients treated with the old standard low-dose cytarabine only.
Updates in Ovarian cancer
In a pooled analysis of women with ovarian cancer, researchers recently published data in the Lancet medical journal trying to answer a long time query in ovarian cancer, whether surgery should be performed first or whether chemotherapy should be used first to shrink the disease. The III EORTC 55971 and CHORUS trials looked at about 1200 patients. Median overall survival was 27.6 months in the neoadjuvant chemotherapy (chemo is given prior to surgery) group vs 26.9 months in the upfront debulking surgery group followed by chemotherapy. It is interesting to note that these patients were followed for about 7-9 years. Most women had Stage II-Stage III disease. Some patients have Stage IV disease and in those patients, Neoadjuvant chemotherapy was associated with better outcomes (24 vs 21 months).
New Breast Cancer treatment
Recent data from the IMpassion130 trial presented at the European Society of medical oncology conference this year has shown how immunotherapy has finally made its foray into breast cancer. In a subtype of triple negative breast tumors. immunotherapy has shown a survival benefit in breast cancer. The result was seen with the anti-programmed cell death ligand 1 (PD-L1) drug atezolizumab (Tecentriq, Genentech) used with chemotherapy in triple negative breast cancer in PD-L1-positive (PD-L1+) patients. There was a 38% improvement in tumor control in the group that had tumors marked by a marker called PD-L1; generally, a marker that predicts response to immunotherapy). In all other patients that had the triple negative disease, the improvement was 20%. This treatment is usually better tolerated than chemotherapy which was the comparator arm.
Q: I have a family member recently diagnosed with ovarian cancer. Should I be worried?
A: I am sorry to hear about cancer in your family. If this is a first degree relative with ovarian cancer; no matter the age of diagnosis this qualifies your family member for hereditary gene testing to evaluate for Hereditary breast and ovarian cancer syndrome. You would only need testing if she is positive for the BRCA mutation which is the most common hereditary gene involved.
Q: I was diagnosed with Stage II colon cancer. Do I really need chemotherapy after my surgery?
A: I’m sorry about your diagnosis. There is no answer that fits for all. Most data does not support the routine use of chemotherapy in Stage II patients. There are some stage II colon cancer patients who are at a higher risk of recurrence and may have about 5% absolute benefit from chemotherapy. Your oncologist will usually be able to determine that based on Colontype Dx testing or something called MSI testing that predicts the response to chemotherapy. Usually, MSI high tumors do not benefit from chemotherapy but the details need to be discussed at a clinic visit with an oncologist.